Hepatic Mitochondrial Defects in a Nonalcoholic Fatty Liver Disease Mouse Model Are Associated with Increased Degradation of Oxidative Phosphorylation Subunits.

Molecular & Cellular Proteomics : MCP
Kwangwon LeeTakhar Kasumov

Abstract

Nonalcoholic fatty liver disease (NAFLD) is associated with hepatic mitochondrial dysfunction characterized by reduced ATP synthesis. We applied the 2H2O-metabolic labeling approach to test the hypothesis that the reduced stability of oxidative phosphorylation proteins contributes to mitochondrial dysfunction in a diet-induced mouse model of NAFLD. A high fat diet containing cholesterol (a so-called Western diet (WD)) led to hepatic oxidative stress, steatosis, inflammation and mild fibrosis, all markers of NAFLD, in low density cholesterol (LDL) receptor deficient (LDLR-/-) mice. In addition, compared with controls (LDLR-/- mice on normal diet), livers from NAFLD mice had reduced citrate synthase activity and ATP content, suggesting mitochondrial impairment. Proteome dynamics study revealed that mitochondrial defects are associated with reduced average half-lives of mitochondrial proteins in NAFLD mice (5.41 ± 0.46 versus 5.15 ± 0.49 day, p < 0.05). In particular, the WD reduced stability of oxidative phosphorylation subunits, including cytochrome b-c1 complex subunit 1 (5.9 ± 0.1 versus 3.4 ± 0.8 day), ATP synthase subunit α (6.3 ± 0.4 versus 5.5 ± 0.4 day) and ATP synthase F(0) complex subunit B1 of complex V (8.5 ± 0.6 vers...Continue Reading

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Citations

Feb 20, 2020·Artificial Cells, Nanomedicine, and Biotechnology·Zhiming ShenShenglin Ge
Jul 1, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Waleska Dornas, Detlef Schuppan
Jan 26, 2020·Journal of Clinical Medicine·Yana SandlersSrinivasan Dasarathy
Dec 20, 2020·Analytical Biochemistry·Andrea Arias-AlvaradoTakhar Kasumov
Jan 9, 2021·Biochimica Et Biophysica Acta. Bioenergetics·Karolina Szczepanowska, Aleksandra Trifunovic
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Feb 16, 2021·World Journal of Hepatology·Elias KouroumalisDimitrios N Samonakis
Jul 3, 2021·International Journal of Molecular Sciences·Inês C M SimõesMariusz R Wieckowski
Jun 19, 2021·Frontiers in Cell and Developmental Biology·Ana Isabel Álvarez-MercadoAraní Casillas-Ramírez
Aug 8, 2021·International Journal of Molecular Sciences·Cheng-Hui WangTzung-Yan Lee
Sep 15, 2021·Critical Reviews in Food Science and Nutrition·Silu HouYaxian Yan
Jan 22, 2022·Briefings in Bioinformatics·Rovshan G Sadygov

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